Endotoxin Exposure and Asthma in ChildrenEPA Grant Number: R834515C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834515
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children
Center Director: Schwartz, David A
Title: Endotoxin Exposure and Asthma in Children
Investigators: Schwartz, David A
Institution: National Jewish Health
EPA Project Officer: Louie, Nica
Project Period: June 22, 2010 through June 21, 2015 (Extended to June 21, 2017)
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Health
Endotoxins are molecules contained in the membrane surrounding the cell wall of certain types of bacteria and become airborne when the bacteria die. Recently, a U.S.-wide survey linked household endotoxin exposure to asthma, making it a U.S. public health concern. However, it is not known whether ambient endotoxin exerts its pathogenic effects on asthma persistence, severity and/or causation. We hypothesize that higher levels of endotoxin exposure cause persistent, problematic asthma and that key environmental (ozone and allergens) and genetic modifiers (variations in the genes coding for endotoxin receptors) contribute to endotoxin susceptibility and pathological asthmatic responses. We propose to study these endotoxin-induced airway conditions in children through three complementary clinical investigations. First, we will capitalize on an ancillary study of a NIH-sponsored multi center cohort of children with asthma (Childhood Asthma Management Program), which has tracked asthma severity for over a decade, to determine if endotoxin exposure, modified by genetics and environment, is associated with greater disease severity and persistence. Second, we propose a panel study of children with asthma to investigate whether endotoxin exposure, modified by environment, is associated with inflamed airways and elevated toll-like receptor (TLR) expression on airway macrophages. TLRs are part of the innate immune system when children are born. Clinically, these inflammatory responses could drive poor asthma control and exacerbations. Finally, we will take advantage of a HUD-sponsored inner-city home intervention study to determine if a home environment intervention will reduce home endotoxin levels and improve asthma.
This combination of studies will provide an understanding of how endotoxin interacts with other potentially toxic exposures in a susceptible child to cause persistent, problematic asthma. These studies will help us to determine the levels of endotoxin exposure that are likely to be problematic for children with asthma, and to develop environmental educational and intervention programs to improve outcomes.
Supplemental Keywords:Endotoxin, exposure, children, asthma, risk, health effects, susceptibility, sensitive populations, genetic pre-disposition, genetic polymorphism, indoor air, dose-response, ozone, remediation, human health, Health, Scientific Discipline, HUMAN HEALTH, Health Risk Assessment, Physiology, Allergens/Asthma, Health Effects, Biology, asthma, sensitive populations, asthma triggers, endotoxin, asthma indices, children, airway inflammation, allergic response
Progress and Final Reports:2010 Progress Report
Main Center Abstract and Reports:R834515 Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834515C001 Endotoxin Exposure and Asthma in Children
R834515C002 Environmental Determinants of Early Host Response to RSV
R834515C003 Environmental Determinants of Host Defense